256
higher than free ERL, further validated by the apoptosis assay. The
relative bioavailability of the complex was approximately 200% in
comparison to pure ERL, additionally confirmed by the enhanced
bioavailability of ERL-NS, in agreement of in vitro dissolution
studies. Therefore inclusion complex of nanosponge with ERL is a
successful approach to increase its solubility and bioavailability
resulting in a reduction in dose and dose-related side effects [49].
Another study exploited the novel stimuli-responsive nanosponges first introduced by Trotta et al. [42] for the targeted delivery and extended release of ERL in lung cancer (Fig. 2). ERL-loaded
nanosponges (ERL-NS) exhibited in vitro-extended drug release,
directly proportional to the external GSH concentration
(76.89 ± 0.1% release at 168 h), thus demonstrating tumor targeting. Additionally, they showed enhanced in vitro cytotoxicity and
97.5% inhibition in tumor growth on administering ERL-NS when
compared to plain ERL (48% inhibition). Cell cytotoxicity study
was evaluated on human lung cancer A549 cell lines. Biodistribution
and in vivo tumor growth inhibition studies revealed drug release
to the cancerous cell, thus preventing unnecessary drug exposure
[50].
Acetyl salicylic acid (ASA) is a nonsteroidal anti-inflammatory and
antipyretic drug which acts by inhibition of prostaglandin synthesis
and is used to relieve the pain. ASA is rapidly hydrolyzed in plasma
to salicylic acid with a half-life of 15–20 min and has a direct irritant effect on gastric mucosa due to inhibition of prostaglandins
causing ulceration, epigastric distress, and hemorrhage. Controlledrelease formulation of ASA would reduce the frequency of administration and the undesired side effects and improve the patient
compliance [51].
β-Cyclodextrin cross-linked with pyromellitic dianhydride NS
was able to complex efficiently with ASA and to release it slowly in
physiological media. These formulations possess nanosize and
spherical shape and display significantly better encapsulation and
stability. The encapsulation efficiency of complex between β-CD
and ASA might depend on different ways of inclusion complex
formation:
– ASA could be hosted inside the CD cavity from the wider side
of the cone-shaped β-CD molecule with the lipophilic benzene
ring going in first and the acetyl group partly standing out of
the cavity.
– ASA could go into CD cavity from wider side with the acetyl
group going in first and benzene ring partly standing out.
– ASA could go into CD cavity from the narrow side with benzene ring going in first and acetyl group partly standing out.
2.2 Cyclodextrin
Nanosponges
for Antiinflammatory Drugs
Maria Tannous et al.
higher than free ERL, further validated by the apoptosis assay. The
relative bioavailability of the complex was approximately 200% in
comparison to pure ERL, additionally confirmed by the enhanced
bioavailability of ERL-NS, in agreement of in vitro dissolution
studies. Therefore inclusion complex of nanosponge with ERL is a
successful approach to increase its solubility and bioavailability
resulting in a reduction in dose and dose-related side effects [49].
Another study exploited the novel stimuli-responsive nanosponges first introduced by Trotta et al. [42] for the targeted delivery and extended release of ERL in lung cancer (Fig. 2). ERL-loaded
nanosponges (ERL-NS) exhibited in vitro-extended drug release,
directly proportional to the external GSH concentration
(76.89 ± 0.1% release at 168 h), thus demonstrating tumor targeting. Additionally, they showed enhanced in vitro cytotoxicity and
97.5% inhibition in tumor growth on administering ERL-NS when
compared to plain ERL (48% inhibition). Cell cytotoxicity study
was evaluated on human lung cancer A549 cell lines. Biodistribution
and in vivo tumor growth inhibition studies revealed drug release
to the cancerous cell, thus preventing unnecessary drug exposure
[50].
Acetyl salicylic acid (ASA) is a nonsteroidal anti-inflammatory and
antipyretic drug which acts by inhibition of prostaglandin synthesis
and is used to relieve the pain. ASA is rapidly hydrolyzed in plasma
to salicylic acid with a half-life of 15–20 min and has a direct irritant effect on gastric mucosa due to inhibition of prostaglandins
causing ulceration, epigastric distress, and hemorrhage. Controlledrelease formulation of ASA would reduce the frequency of administration and the undesired side effects and improve the patient
compliance [51].
β-Cyclodextrin cross-linked with pyromellitic dianhydride NS
was able to complex efficiently with ASA and to release it slowly in
physiological media. These formulations possess nanosize and
spherical shape and display significantly better encapsulation and
stability. The encapsulation efficiency of complex between β-CD
and ASA might depend on different ways of inclusion complex
formation:
– ASA could be hosted inside the CD cavity from the wider side
of the cone-shaped β-CD molecule with the lipophilic benzene
ring going in first and the acetyl group partly standing out of
the cavity.
– ASA could go into CD cavity from wider side with the acetyl
group going in first and benzene ring partly standing out.
– ASA could go into CD cavity from the narrow side with benzene ring going in first and acetyl group partly standing out.
2.2 Cyclodextrin
Nanosponges
for Antiinflammatory Drugs
Maria Tannous et al.